N-(benzylsulfonyl)-D-phenylalanine | 177583-41-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(benzylsulfonyl)-D-phenylalanine
• 英文别名: N-(Phenylmethanesulfonyl)-D-phenylalanine；(2R)-2-(benzylsulfonylamino)-3-phenylpropanoic acid
• CAS: 177583-41-4
• 化学式: C₁₆H₁₇NO₄S
• 分子量: 319.381
• InChiKey: ICFOBMSVJMGIMX-OAHLLOKOSA-N

物化性质

• 沸点：
  532.0±60.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(benzylsulfonyl)-D-phenylalanine 在 PS-carbodiimide resin 、 茴香硫醚 、 PS-DIEA resin 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.25h， 生成 (S)-3-Cyano-N-[(S)-4-guanidino-1-(thiazole-2-carbonyl)-butyl]-2-((R)-3-phenyl-2-phenylmethanesulfonylamino-propionylamino)-propionamide
  参考文献：
  名称：

  Polymer-Assisted Solution-Phase Library Synthesis and Crystal Structure of α-Ketothiazoles as Tissue Factor VIIa Inhibitors

  摘要：

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification concepts, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multistep synthesis affords desired alpha-ketothiazole products in excellent purities and yields. A variety of L-amino acid inputs were used to probe the S-2 pocket of tissue Factor VIIa enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10k bound to the TF/ VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue Factor VIIa, with some analogues demonstrating selectivity over thrombin.

  DOI：

  10.1021/jm030130t
• 作为产物：
  描述：

  D-phenylalanine hydrochloride 、 苄磺酰氯 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-(benzylsulfonyl)-D-phenylalanine
  参考文献：
  名称：

  新型非共价凝血酶抑制剂掺入P（1）4,5,6,7-四氢苯并噻唑精氨酸侧链模拟物。

  摘要：

  描述了一系列新型的基于非共价D-Phe-Pro-Arg主题的凝血酶抑制剂的设计，合成和生物学活性，该抑制剂结合了4,5,6,7-四氢苯并噻唑-2-胺作为新型的精氨酸替代物。一系列凝血酶抑制剂中最有效的化合物9的体外K（i）为128 nM，对胰蛋白酶的选择性为342倍。基于与人α-凝血酶共结晶的化合物9的X射线晶体结构，讨论了这类新型凝血酶抑制剂在酶活性位点的结合方式。

  DOI：

  10.1016/j.ejmech.2003.12.006

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20030191139A1

  公开（公告）日：2003-10-09

  The invention relates to compounds of formula I D—CO—B—A-Het and pharmaceutically acceptable salts thereof where substituents in description have the specified meanings. The compounds are used as thrombin inhibitors.

  该发明涉及公式I的化合物D—CO—B—A-Het及其药用可接受的盐，其中描述中的取代基具有指定的含义。这些化合物被用作凝血酶抑制剂。
• Polymer-Assisted solution-Phase (PASP) parallel synthesis of an α-Ketothiazole library as tissue factor VIIa inhibitors
  作者：Michael S South、Thomas A Dice、Thomas J Girard、Rhonda M Lachance、Anna M Stevens、Roderick A Stegeman、William C Stallings、Ravi G Kurumbail、John J Parlow

  DOI：10.1016/s0960-894x(03)00398-6

  日期：2003.7

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-L-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification protocols, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multi-step synthesis affords the desired alpha-ketothiazole products in excellent purities and yields. A variety Of L-amino acid inputs were used to probe the S2 pocket of the tissue factor (TF) Vila enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10e bound to the TF/VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue factor VIIa, with some analogues demonstrating selectivity versus thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.
• THROMBIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP0772590B1

  公开（公告）日：2002-10-09
• US5510369A
  申请人：——

  公开号：US5510369A

  公开（公告）日：1996-04-23
• US5714485A
  申请人：——

  公开号：US5714485A

  公开（公告）日：1998-02-03